Laboratório de Química Aplicada à Bioativos (LaQuiABio), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Laboratório de Neuroquímica, Inflamação e Câncer (Neurocan), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Metab Brain Dis. 2022 Aug;37(6):2053-2059. doi: 10.1007/s11011-022-01005-5. Epub 2022 May 26.
The aim of the present study was to evaluate the anti-glioma activity of 3-(4-fluorobenzyl)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (AV23) in a preclinical model of glioblastoma, as well as behavioral parameters and toxicological profile. The implantation of C6 cells in the left striatum of male Wistar rats was performed by stereotaxic surgery. After recovery, animals were treated with vehicle (canola oil) or AV23 (10 mg/kg/day) intragastrically for 15 days. It was found that AV23 reduced tumor volume by 90%. Serum biochemical parameters such as triglycerides, cholesterol, HDL-cholesterol, LDL-cholesterol, albumin, aspartate aminotransferase, urea, creatinine and total proteins were not changed; however, there was a slight increase in alanine aminotransferase. The compound AV23 reverted the hypoglycemia and the reduction in body weight caused by glioblastoma. Additionally, AV23 was able to revert the reduction of locomotion caused by the tumor implantation. Therefore, the compound AV23 can be considered a promising candidate in the treatment of glioblastoma.
本研究旨在评估 3-(4-氟苄基)-5-(4-甲氧基苯亚甲基)噻唑烷-2,4-二酮(AV23)在胶质母细胞瘤的临床前模型中的抗神经胶质瘤活性,以及行为参数和毒理学特征。通过立体定向手术将 C6 细胞植入雄性 Wistar 大鼠的左侧纹状体。恢复后,动物通过灌胃接受载体(菜籽油)或 AV23(10mg/kg/天)治疗 15 天。结果发现,AV23 使肿瘤体积减少了 90%。血清生化参数如甘油三酯、胆固醇、HDL-胆固醇、LDL-胆固醇、白蛋白、天冬氨酸氨基转移酶、尿素、肌酐和总蛋白没有改变;然而,丙氨酸氨基转移酶略有增加。化合物 AV23 逆转了神经胶质瘤引起的低血糖和体重减轻。此外,AV23 能够逆转肿瘤植入引起的运动减少。因此,化合物 AV23 可被视为治疗神经胶质瘤的有前途的候选药物。